Hyperemesis Gravidarum
Hyperemesis Gravidarum (HG) is considered the most severe form of NVP, affecting almost every aspect of a woman’s life (and her family’s) for weeks – usually months. In women with HG, nausea and vomiting is unrelenting, constant, and debilitating.
No amount or method of eating, drinking, sleeping, or distraction can completely ease symptoms – if at all – and in most cases, medications work only mildly or all too temporarily.
HG is a condition that needs to be managed hour-by-hour; it can result in repeat emergency department visits as well as hospitalizations.
Physical, emotional, and mental health support, as well as recognition of the condition by family, friends, and health care providers (HCPs) is critical in the prevention of serious complications, some of which can be life-threatening.
Women with HG – or even severe NVP symptoms – need to be an advocate for themselves. Women should call their HCP anytime they experience the complications described below – and even earlier if they are having trouble physically, emotionally, or mentally coping with their symptoms. Research is beginning to show just how important early management is in the prevention of more serious complications.
Background
Hyperemesis ("excessive vomiting") Gravidarum ("during pregnancy") (HG) is the most extreme form of NVP, characterized by endless and severe nausea and vomiting. Many women with HG describe it as the worst experience of their lives, as the condition often progresses into a cascade of physical, mental, and emotional complications that all require support from women's partners, families, friends, and HCPs.
HG is a real, and potentially life-threatening condition that can be absolutely incapacitating. HG is the most common reason for hospitalization in the first half of pregnancy due to constant nausea and intractable vomiting.
HG is considered a rare disorder estimated to affect up to 3% of pregnancies; a range of up to 10% of all pregnancies has also been reported. This higher range is possible as women are often misdiagnosed or overlooked as having severe "normal" NVP as opposed to HG (read Severity, NVP vs. HG)
There is no international agreement on the exact definition of HG. Therefore, diagnosis is made based on an assessment of a variety of signs and symptoms and at the discretion of an HCP. This makes studying the overall condition, along with its prevalence, complications, and related outcomes very difficult, as well as the best recommendations for optimal management.
Diagnosis
Although no consistent definition exists, it is most often defined as the occurrence of greater than three episodes of vomiting per day, ketones in the urine, more than 5% of body weight loss, muscle contractions and wasting, low potassium, malnutrition, dehydration, and electrocardiographic (heart) abnormalities.
Along with a physical assessment, an HCP will also request blood and urine tests along with a possible ultrasound to rule out molar pregnancy or multiple gestation.
Not all factors above need to be present for a diagnosis, and current research indicates the presence of ketones is not necessarily a good indicator of symptom severity.
The liver turns fat into ketones when the body lacks glucose/insulin from regular food intake; this occurs through starvation or carbohydrate restriction. As such, it was often used a prime indicator for NVP severity, but is no longer completely necessary for diagnosis.
A diagnosis of HG does not mean the symptoms will be present the entire pregnancy, although it is possible (it is also possible for milder NVP symptoms to last 9 months). In general, HG symptoms have a similar rise and fall to "standard" NVP with a good possibility for relief beginning around mid-pregnancy. For women who have symptoms their entire pregnancy, they should experience almost complete relief after delivery.
Causes
HG is generally regarded as a disease of unknown causes, as progress regarding its etiology has been slow. Although pregnancy itself is technically the cause, the mechanisms by which pregnancy leads to HG (or NVP) is not known. This is mostly due to the only recent understanding that HG is not a psychological condition; only in the last two to three decades have researchers begun to look for measurable physiological causes.
Despite the above, as of April 2022, the leading potential cause behind the development of HG is abnormalities within a particular gene and its variants: GDF15.
In a study published in February 2022, GDF15 was the greatest genetic risk factor for HG, corroborating prior evidence. "GDF15 is most highly expressed by the placenta, increases significantly in the first trimester and activates the vomiting center" of the brain.
It is also currently assessed women likely experience several variables in early pregnancy that lead to the development of HG, similar to NVP, albeit more extreme. These can include, but are not limited to: acid reflux, thyroid and gastrointestinal dysfunction, severe constipation, hormone sensitivity, extreme fatigue, and possible genetic variants (read Causes and Contributing Factors for more detailed information).
The placenta and its hormones may play a much larger role in HG than NVP, based on almost complete symptom relief upon delivery (similarly to preeclampsia). However, as stated above, more research is needed, and associations between HG and placental disorders or preeclampsia are inconsistent.
Symptoms and Complications
Nausea and vomiting are almost never the only symptoms women with HG experience. HG has an extensive list of additional symptoms and complications that are compounding and progressive. Although not all women will experience these complications, they can include:
Debilitating fatigue
Severe dehydration
Gastric irritation/trauma
Ketosis
Muscle weakness
Malnutrition
Bowel obstruction
Kidney stones/kidney failure
Excess saliva
Preterm labor
Adverse psychological effects
Financial burden
Posttraumatic stress disorder
Depression
Retinal hemorrhage (from vomiting)
Mallory-Weiss tears (esophageal tear)
Jaundice (liver failure)
A list of mild to moderate complications of NVP can be read here.
Thyrotoxicosis: A condition caused by hyperthyroidism, an excess of thyroid hormone in the blood; it is estimated that up to two-thirds of HG patients have hyperthyroidism, which is easily screened for and treated (may not always relieve symptoms, but still needs to be treated).
Electrolyte imbalance (potassium, calcium, iron, folate and other B vitamins): If potassium levels drop too low, this is known as hypokalemia and can result in cardiac arrest when severe. Thiamin (B1) can be depleted in a matter of weeks, resulting in Wernicke’s encephalopathy, a neurological condition resulting in repetitive, uncontrolled eye movements (nystagmus), loss of control of body movements (ataxia), and confusion. As of 2016, Wernicke’s encephalopathy has been reported to be on the rise in HG patients.
The management of electrolytes/thyroid hormones in women with HG is critical in the avoidance of catastrophic complications which includes maternal death. In a 2016 study that evaluated six HG deaths, causes were attributed to hypokalemia, Wernicke’s encephalopathy, and/or thyrotoxicosis.
A Lack of Recognition: Despite current research, many HCPs and family members still do not give the condition or its symptoms enough serious attention, or they trivialize how the woman is feeling and any help she may need.
If women's symptoms are recognized and acknowledged by their HCPs, partners, and family members, and women and their partners learn to recognize when she needs medical care, this can result in immediate and necessary treatment – as well as the prevention of serious and potentially life-threatening complications such as those described above.
Hospitalization: In the United States, more than 36,000 women are admitted to the hospital each year due to HG, not including numerous emergency department visits. HG is the most common reason for hospitalization in the first half of pregnancy, and second overall to only preterm labor.
Women are often treated with intravenous fluids, electrolytes, and antiemetics. Serious cases may require enteral (nasal gastric tube) or total parenteral nutrition (read more).
HG is very difficult to manage, and management is usually temporary until women return to the Emergency Department (ED) for additional medical care. Unfortunately, there are no consistent guidelines for ED HCPs attending to women with HG. The care that women receive is highly dependent on the HCP during that visit.
Further, researchers have expressed concern that with a trend toward a decrease in hospitalization for HG and an increase in outpatient and emergency department management of symptoms, there may be an increase in HG-related complications and deaths in the future.
Fetal Effects of HG
Women with HG tend to have more extreme symptoms and malnutrition for longer periods than more mild forms of NVP; however, research regarding physical or developmental adverse effects on a baby born to a woman with HG are conflicting.
Some studies have indicated a higher risk of colic, irritability, growth restriction, low birth weight, and various birth defects, but others have found no association and indicate that women with HG should be reassured their infant will very likely be born healthy (read Fetal Effects of NVP/HG).
Mental Health
Mental health complications occur as a direct result of HG and they cannot be underestimated. HG is considered a risk factor for depression during and after pregnancy. Women should not be afraid to seek help even after delivery.
HG can be traumatic and some women can experience posttraumatic stress symptoms, as well as signs as of anxiety and depression, sometimes years later. Some studies have reached this conclusion even with more mild or moderate cases.
Fighting nausea weeks on end is physically draining, mentally challenging, and utterly stressful when relationships become strained during the process. Even when there is whole and complete understanding among family and friends, frustration can occur when no one knows what to do or how to help.
The overall impact of HG on a woman's mental health depends on her support system, her employer, whether she takes care of other family members, her day-to-day responsibilities, as well as the severity of her symptoms, her HCP's recognition of the condition, and many other factors.
Survey results of 216 qualified GPs (General Practitioners) and GP trainees in Wales, United Kingdom, published in November 2021 determined that only 19% of participants routinely screened for signs of mental health complications with HG and prior experience/education did not increase likelihood of this happening.
Current/Future Pregnancies
NVP in general is often indicated as a “self-limiting” condition, a condition that is essentially limited only by the action of the individual; it will eventually go away on its own, with no lasting ill-effects. However, this definition cannot apply when NVP/HG ends a current pregnancy or prevents a pregnancy in the future.
A study published in March 2019 reported that women received insensitive or even hurtful remarks from their HCPs, and as a result of their overall experience, several study participants did not wish to become pregnant again.
Further, numerous studies and reviews have indicated women with NVP /HG considered termination or have terminated a wanted pregnancy due to the extreme severity of their symptoms. Women have also decided against a future pregnancy for the same reason.
These consequences are life-changing and life-lasting, and illustrate the important of sincere recognition and aggressive management by family, friends, and HCPs.
Recurrence
Fortunately, recurrence does not always occur in a subsequent pregnancy. However, due to the difficulties in studying HG, recurrence rates are far from precise. A December 2019 study attempting to determine a more accurate recurrent rate could only determine a range of 15% to 81%. A smaller, more narrow range could not be determined based on inconsistent definition and small sample sizes.
A study published in May 2021 found that 35 women with a history of HG became pregnant again; 14 of these women had postponed their pregnancy due to HG. HG recurred in 89% of pregnancies. One woman terminated and eight women (23%) considered terminating their pregnancy because of recurrent HG. Further, twenty-four out of 38 women did not get pregnant again because of HG in the past.
Women with a history of HG who wish to have another pregnancy are often recommended to plan ahead regarding resources, family functioning and logistics, and to have a solid medical plan of action if HG recurs in a subsequent pregnancy.
Management
Women with HG require constant management, care, and monitoring. Further, women may need to employ a variety of different dietary changes, lifestyle modifications, mental health strategies, medications, and frequent discussions with their HCP and family members – at the same time.
Although the management of HG symptoms specifically can feel like an impossibly hopeless task, women should not aim for major or complete relief, but for small, gradual reductions of symptoms long enough to experience even the shortest of breaks.
Action
Women with HG – or even severe NVP symptoms – need to be an advocate for themselves. Women do not need to suffer through this experience alone or without appropriate medical help. Women, and their partners, should find an HCP who understands this condition and empathizes with women who are going through it.
Women should call their HCP anytime they experience the complications described above – and even earlier if they are having trouble physically, emotionally, or mentally coping with their symptoms. Research is beginning to show just how important early management is in the prevention of more serious complications.
In addition, women should call their HCP immediately if they:
Experience severe nausea, vomiting, abdominal pain, and/or weight loss
See blood in vomit, which could be red or black
Cannot keep fluids down; experience symptoms of dehydration (above)
Pass only a small amount of urine or urine is a dark color
Have a fever
Have a rapid heart rate
Experience dizziness, faintness, tiredness, or confusion
Women should consider sharing their experience (below) with HG during pregnancy. These experiences are incredibly valuable for other women, especially those trying to learn about the condition and how other women may have coped or managed their symptoms.
It is important for women currently experiencing HG to recognize they are not alone and other women can teach them how to better advocate for themselves when they are suffering such severe symptoms.
Partners/Support
HG is a very physically, mentally, and emotionally difficult condition during pregnancy – for both pregnant women who experience it, and families who help her through it.
This condition can frustrate everyone involved; it can be very painful to watch the woman suffer these debilitating effects, yet family members often feel completely helpless.
Partners/support should:
Learn all about the condition, as well as general NVP
Recognize the condition is real
Understand that very little can be done to ease symptoms
Partners/support should focus on taking over her normal day-to-day responsibilities so she can focus solely on her health
If the woman had HG in a previous pregnancy, family members should help her prepare for it in a subsequent pregnancy
Of most importance, partners and family members may often be the first individuals to notice a woman needs medical help. Further, communication difficulties can be an early sign of WE, and seizures may also occur.
Resources
HER Foundation (Hyperemesis Education and Research)
The International Collaboration for Hypermesis Gravidarum Research
Pregnancy Sickness Support (United Kingdom)
Hyperemesis Gravidarum Australia
Nausea and Vomiting of Pregnancy: Committee Opinion 189; January 2018 (American College of Obstetricians and Gynecologists)
Morning Sickness: Nausea and Vomiting of Pregnancy (American College of Obstetricians and Gynecologists)
Pregnancy sickness (nausea and vomiting of pregnancy and hyperemesis gravidarum) (Royal College of Obstetricians and Gynecologists)